Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain.
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ABSTRACT:
SUBMITTER: Song G
PROVIDER: S-EPMC7609633 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bone is a dynamic organ continuously undergoing shaping, repairing and remodeling. The homeostasis of bone is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts (OCs) are specialized multinucleated cells derived from hematopoietic stem cells (HSCs) or monocytes/macrophage progenitor cells. There are different stages during osteoclastogenesis, and one of the most important steps to form functional osteoclasts is realized by cell-cell fusion. In our study, microarray was performed to detect the expression profiles of lncRNA, mRNA, circRNA and miRNA at different stages during osteoclastogenesis of RAW264.7 cells. Often changed RNAs were selected and clustered among the four groups with Venn analysis. The results revealed that expressions of 518 lncRNAs, 207 mRNAs, 24 circRNAs and 37 miRNAs were often altered at each stage during OC differentiation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis were performed to predict the functions of differentially expressed lncRNAs and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed RNAs. The present study provided a systematic perspective on the potential function of non-coding RNAs (ncRNAs) during osteoclastogenesis.
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Project description:BACKGROUND This study aimed to identify significantly altered circRNAs/lncRNAs/miRNAs/mRNAs pathways in preeclampsia (PE), investigate their target relationships, and determine their biological functions. MATERIAL AND METHODS Base on RNA-seq technique and the GEO database, expression profiles of circRNAs/lncRNAs/miRNAs/mRNAs related to PE were obtained. Differentially expressed RNAs were determined using the Limma package in R. Gene set enrichment analysis (GSEA) was performed using GSEA software (v. 3.0) and illustrated by ClusterProfiler and ggplot2 package in R. DAVID database (v. 6.8) was implemented to analyze functional categories and the association between genes and the corresponding Gene Ontology (GO) classification. The R visualization package GOPlot was used to get a better visualization of the relationships between genes and the selected functional categories. CeRNA networks which visualized the correlations between circRNA/lncRNA-miRNA-mRNA were constructed using Cytoscape software (v. 3.6.0). Targetscan and miRanda database were used to predict target relationships between circRNA/lncRNA-miRNA-mRNA. QRT-PCR and luciferase reporter assay were used to verify the expression and target relationship of has_circ_0088196/LINC01492/miR-100-5p/LIF (leukemia inhibitory factor). RESULTS The jak-stat signaling pathway was activated and miR-100-5p was downregulated in PE compared with normal tissues both in collected placental tissue samples and GEO database. Upregulated LIF, LINC01492, and hsa_circ_0088196 were negatively correlated with miR-100-5p expression and had a targeted relationship with miR-100-5p. CONCLUSIONS miR-100-5p may suppress PE development, while LIF, LINC01492, and hsa_circ_0088196 may promote it though inhibiting miR-100-5p. The jak-stat signaling pathway was activated and involved in PE progression.
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Project description:To systematically evaluate the whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer, we performed whole-transcriptome sequencing based on the tumorous (C) and their corresponding non-tumorous adjacent to the tumors (CP) from eight CHOL patients. Subsequently, differential expression analysis was performed on the C and CP groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in CHOL. In addition, The Cancer Genome Atlas (TCGA) for CHOL data was used to validate the results. In total, 2,895 differentially expressed messenger RNAs (dif-mRNAs), 56 differentially expressed microRNAs (dif-miRNAs), 151 differentially expressed long non-coding RNAs (dif-lncRNAs), and 110 differentially expressed circular RNAs (dif-circRNAs) were found in CHOL samples compared with controls. Enrichment analysis on those differentially expressed genes (DEGs) related to miRNA, lncRNA, and circRNA also identified the function of spliceosome. The downregulated hsa-miR-144-3p were significantly enriched in the competing endogenous RNA (ceRNA) complex network, which also included 7 upregulated and 13 downregulated circRNAs, 7 upregulated lncRNAs, and 90 upregulated and 40 downregulated mRNAs. Moreover, most of the DEGs and a few of the miRNAs (such as hsa-miR-144-3p) were successfully validated by TCGA data. The genes involved in RNA splicing and protein degradation processes and miR-144-3p may play fundamental roles in the pathogenesis of CHOL.
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Project description:BackgroundAdult degenerative scoliosis (ADS) is forecast to be a prevalent disabling condition in an aging society. Universally, its pathogenesis is perceived as intervertebral disc degeneration (IDD), however, a thought-provoking issue is why precisely a subset of patients with disc degeneration develop ADS. Exploring the diversities between common IDD and ADS would contribute to unraveling the etiological mechanisms of ADS. Therefore, we aimed to integrate the circRNA, lncRNA, miRNA, and mRNA expression profiles from normal adults (Normal), patients with lumbar disc herniation (LDH), and ADS by whole transcriptome sequencing, which identifies critical functional ncRNA and ceRNA networks and crosstalk between the various transcripts.MethodsThe fresh whole blood samples (n = 3/group) were collected from ADS patients, LDH patients, and healthy volunteers (Normal group), which were examined for mRNA, miRNA, lncRNA, and circRNA expression and screened for differentially expressed (DE) ncRNAs. Then, Gene Ontology (GO) and KEGG analyses were performed for gene annotation and enrichment pathways on the DE RNAs, which were constructed as a lncRNA-miRNA-mRNA network. Eventually, DE RNAs were validated by qRT-PCR targeting disc nucleus pulposus (NP) tissue in ADS and LDH group (n = 10/group).ResultsCompared to the LDH group, we identified 3322 DE mRNAs, 221 DE lncRNAs, 20 DE miRNAs, and 15 DE circRNAs in the ADS. In contrast to Normal, 21 miRNAs and 19 circRNAs were differentially expressed in the ADS. The expression of multiple differentially expressed ncRNAs was confirmed by qRT-PCR analysis to be consistent with the sequencing results. In addition, GO, and KEGG analysis demonstrated that most DE mRNAs and ncRNAs target genes are involved in various biological processes, including Endocytosis, Apoptosis, Rap1 signaling pathway, Notch signaling pathway, and others. The constructed lncRNA-miRNA-mRNA co-expression network was primarily related to angiogenesis and regulation.ConclusionBy focusing on comparing asymmetric and symmetric disc degeneration, whole-transcriptome sequencing and bioinformatics analysis systematically screened for key ncRNAs in the development of ADS, which provided an abundance of valuable candidates for the elucidation of regulatory mechanisms. The DE ncRNAs and the lncRNA-miRNA-mRNA network are intrinsically involved in the regulation of mediator and angiogenesis, which may contribute to the insight into the pathogenesis of ADS.
| S-EPMC10098162 | biostudies-literature
Project description:Diabetic nephropathy is a lethal disease that can lead to chronic kidney disease and end-stage kidney disease. Exosomes, which are nanosized extracellular vesicles, are closely involved in intercellular communication. Most importantly, exosomes play critical roles in disease occurrence and development. However, the function of exosomes in diabetic nephropathy progression has not been fully elucidated. In the present study, we determined the expression profiles and differences of lncRNAs, mRNAs, circRNAs and miRNAs in exosomes derived from human renal tubular epithelial cells with or without high glucose (HG) treatment. A total of 169 lncRNAs, 885 mRNAs, 3 circRNAs and 152 miRNAs were differentially expressed in exosomes secreted by HG-challenged HK-2 cells (HG group) compared with controls (NC group). The functions of differentially expressed mRNAs, mRNAs colocalized or coexpressed with differentially expressed lncRNAs (DElncRNAs), potential target genes of miRNAs and source genes of circRNAs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. According to these differentially expressed RNAs, we established an integrated circRNA-lncRNA-miRNA-mRNA regulatory network. In conclusion, our study suggested that exosomal lncRNAs, mRNAs, circRNAs and miRNAs participate in the progression of diabetic nephropathy and may be possible biomarkers and therapeutic targets in diabetic nephropathy.
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Project description:In response to muscle injury, muscle stem cells are stimulated by environmental signals to integrate into damaged tissue to mediate regeneration. L-leucine (L-leu), a branched-chain amino acid (BCAA) that belongs to the essential amino acids (AAs) of the animal, has gained global interest on account of its muscle-building and regenerating effects. The present study was designed to investigate the impact of L-leu exposure to promote the proliferation of equine skeletal muscle satellite cells (SCs) on the regulation of RNA networks, including mRNA, long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA), and microRNA (miRNA) in skeletal muscles. Equine SCs were used as a cell model and cultured in different concentrations of L-leu medium. The cell proliferation assay found that the optimal concentration of L-leu was 2 mM, so we selected cells cultured with L-leu concentrations of 0 mM and 2 mM for whole-transcriptiome sequencing, respectively. By high-throughput sequencing analysis, 2470 differentially expressed mRNAs (dif-mRNAs), 363 differentially expressed lncRNAs (dif-lncRNAs), 634 differentially expressed circRNAs (dif-circRNAs), and 49 differentially expressed miRNAs (dif-miRNAs) were significantly altered in equine SCs treated with L-leu. To identify the function of autoimmunity and anti-inflammatory responses after L-leu exposure, enrichment analysis was conducted on those differentially expressed genes (DEGs) related to lncRNA, circRNA, and miRNA. The hub genes were selected from PPI Network, including ACACB, HMGCR, IDI1, HAO1, SHMT2, PSPH, PSAT1, ASS1, PHGDH, MTHFD2, and DPYD, and were further identified as candidate biomarkers to regulate the L-leu-induced proliferation of equine SCs. The up-regulated novel 699_star, down-regulated novel 170_star, and novel 360_mature were significantly involved in the competing endogenous RNA (ceRNA) complex network. The hub genes involved in cell metabolism and dif-miRNAs may play fundamental roles in the L-leu-induced proliferation of equine SCs. Our findings suggested that the potential network regulation of miRNAs, circ-RNAs, lncRNAs, and mRNAs plays an important role in the proliferation of equine SCs, so as to build up new perspectives on improving equine performance and treatment strategies for the muscle injuries of horses.
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Project description:BackgroundGlucocorticoids (GCs) are commonly used to treat autoimmune diseases and malignancies in children and adolescents. Growth retardation is a common adverse effect of GC treatment in pediatric patients. Accumulating evidence indicates that non-coding RNAs (ncRNAs) are involved in the pathogenesis of glucocorticoid-induced growth retardation (GIGR), but the roles of specific ncRNAs in growth remain largely unknown.MethodsIn this study, 2-week-old male Sprague-Dawley rats had been treated with 2 mg/kg/d of dexamethasone for 7 or 14 days, after which the growth plate tissues were collected for high-throughput RNA sequencing to identify differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in GIGR rats.ResultsTranscriptomic analysis identified 1,718 mRNAs, 896 lncRNAs, 60 circRNAs, and 72 miRNAs with different expression levels in the 7d group. In the 14d group, 1,515 mRNAs, 880 lncRNAs, 46 circRNAs, and 55 miRNAs with differential expression were identified. Four mRNAs and four miRNAs that may be closely associated with the development of GIGR were further validated by real-time quantitative fluorescence PCR. Function enrichment analysis indicated that the PI3K-Akt signaling pathway, NF-kappa B signaling pathway, and TGF-β signaling pathway participated in the development of the GIGR. Moreover, the constructed ceRNA networks suggested that several miRNAs (including miR-140-3p and miR-127-3p) might play an important role in the pathogenesis of GIGR.ConclusionsThese results provide new insights and important clues for exploring the molecular mechanisms underlying GIGR.
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Project description:We carried out whole transcriptome sequencing (WTS) on the tumor and the matching adjacent normal tissues from five patients having Xp11 translocation renal cell carcinoma (RCC). This was performed in terms of obtaining more understanding of the genomic panorama and molecular basis of this cancer. To examine gene-regulatory networks in XP11 translocation RCC, variance expression analysis was carried out, followed by functional enrichment analysis. Gene Expression Omnibus (GEO) of Xp11 translocation RCC data was used to validate the results. As per inclusion criteria, a total of 1886 differentially expressed mRNAs (DEmRNAs), 56 differentially expressed miRNAs (DEmiRNAs), 223 differentially expressed lncRNAs (DElncRNAs), and 1764 differentially expressed circRNAs (DEcircRNAs) were found. KEGG enrichment study of DEmiRNA, DElncRNA, and DEcircRNA target genes identified the function of protein processing in the endoplasmic reticulum, lysosome, and neutrophil-mediated immunity. Three subnetwork modules integrated from the PPI network also revealed the genes involved in protein processing in the endoplasmic reticulum, lysosome, and protein degradation processes, which may regulate the Xp11 translocation RCC process. The ceRNA complex network was created by Cytoscape, which included three upregulated circRNAs, five upregulated lncRNAs, 24 upregulated mRNAs, and two downregulated miRNAs (hsa-let-7d-5p and hsa-miR-433-3p). The genes as a prominent component of the complex ceRNA network may be key factors in the pathogenesis of Xp11 translocation RCC. Our findings clarified the genomic and transcriptional complexity of Xp11 translocation RCC while also pointing to possible new targets for Xp11 translocation RCC characterization.
| S-EPMC10047933 | biostudies-literature
Project description:Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1789 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma. We hope to inspire researchers to study the role of non-coding RNAs in glioblastoma.
2016-08-30 | GSE86202 | GEO
Project description:Testicular development is a tightly regulated process in mammals. Understanding the molecular mechanisms of yak testicular development will benefit the yak breeding industry. However, the roles of different RNAs, such as mRNA, lncRNA, and circRNA in the testicular development of yak, are still largely unclear. In this study, transcriptome analyses were performed on the expression profiles of mRNAs, lncRNAs, and circRNAs in testis tissues of Ashidan yak at different developmental stages, including 6-months-old (M6), 18-months-old (M18), and 30-months-old (M30). A total of 30, 23, and 277 common differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in M6, M18, and M30, respectively. Furthermore, functional enrichment analysis showed that the common DE mRNAs during the entire developmental process were mainly involved in gonadal mesoderm development, cell differentiation, and spermatogenesis processes. Additionally, co-expression network analysis identified the potential lncRNAs related to spermatogenesis, e.g., TCONS_00087394 and TCONS_00012202. Our study provides new information about changes in RNA expression during yak testicular development, which greatly improves our understanding of the molecular mechanisms regulating testicular development in yaks.
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